The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.
Venomous animals produce venom rich in bioactive components that have evolved to specifically and potently modulate a wide range of ion channels and receptors. Due to these exquisite properties, venom components have found use in the treatment and management of several conditions. For example, the analgesic drug Prialt is a peptide from the venom of the marine cone snail Conus magus. 
Spider venoms are predominantly comprised of peptides, with some venoms containing greater than 1000 novel peptides. These venoms contain a significant number of peptides that modulate the activity of neuronal ion channels and receptors, such as voltage-gated potassium (Kv), calcium (Cav) and sodium (Nav) channels, which is not surprising due to the paralytic function of spider venom (Saez, et al. (2010) Toxins, 2:2851-71).
Spider venom peptides typically adopt an inhibitor cystine knot conformation, which provides them with extraordinary chemical, thermal and biological stability. The inhibitor cystine knot comprises a ring formed by two disulfide bonds and the intervening peptide backbone, with a third disulfide bond piercing the ring, forming a pseudo-knot. The stability resulting from this conformation is advantageous for the development of peptide therapeutics.
Voltage-gated sodium channels (Nav) are complex transmembrane proteins comprised of a pore-forming α-subunit and accessory β-subunits that play an essential role in the initiation and propagation of action potentials in excitable cells. Nav channels open to permit influx of sodium ions when the membrane potential is depolarized and close on repolarization. They also close on continuous depolarization by a process termed inactivation, which leaves the channel refractory (i.e. unable to open again for a period of time).
To date, apart from the related Nax, which has been suggested to function as a sodium sensor (Shimizu, et al. (2007) Neuron, 54(1): 59-72; Hiyama, et al. (2002) Nat Neurosci, 5(6): 511-512), nine isoforms termed Nav1.1-Nav1.9 have been functionally defined as sodium-selective ion channels (Yu and Catterall (2003) Genome Biol, 4(3): 207). Their distinct tissue distribution as well as amenability to modulation by toxins and drugs has led to significant interest in Nav channels as therapeutic targets in a number of poorly treated conditions, ranging from epilepsy to cardiac arrhythmias and pain (Clare, et al. (2000) Drug Discov Today, 5(11): 506-520).
Of particular interest is Nav1.7, as loss-of-function mutations in humans lead to congenital insensitivity to pain, a rare condition that results in an inability to sense pain (Ahmad, et al. (2007) Hum. Mol. Genet., 16:2114-2121; Cox, et al. (2006) Nature, 444:894-898). Accordingly, pharmacological inhibition of Nav1.7 is an exciting therapeutic strategy for the treatment of a wide range of pain types including inherited erythromelalgia and paroxysmal extreme pain disorder, two conditions whose pathophysiology arises from Nav1.7 gain-of-function mutations. Nav1.7 selectivity is key to developing more effective analgesics as activity at major off-targets, including the skeletal muscle isoform Nav1.4, the cardiac isoform Nav1.5, as well as neuronal isoforms Nav1.1, Nav1.2 and Nav1.6, is likely to impact on the therapeutic window and cause dose-limiting adverse effects (Trimmer, et al. (1990) Dev. Biol., 142:360-367; Rogart, et al. (1989) Proc. Natl. Acad. Sci. USA, 86:8170-8174; Caldwell, et al. (2000) Proc. Natl. Acad. Sci. USA, 97:5616-5620). However, achieving sufficient selectivity for Nav1.7 over the other Nav isoforms is challenging due to the high sequence homology within the Nav family (Catterall, et al. (2005) Pharmacol. Rev., 57:397-409).
Accordingly, there exists a need for new Nav inhibitors with greater selectivity for Nav1.7 than the other Nav isoforms and which may be used for treating or preventing conditions associated with Nav1.7 activity.